Hyponatremia and Worsening Sodium Levels Are Associated With Long‐Term Outcome in Patients Hospitalized for Acute Heart Failure

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Abstract

Background

Hyponatremia predicts poor prognosis in patients with acute heart failure ( AHF). However, the association of the severity of hyponatremia and changes of serum sodium levels with long‐term outcome has not been delineated.

Methods and Results

The study population was drawn from the HARVEST registry ( Heart F ailure Registry of Taipei Veteran s General Hospi tal), so that patients hospitalized for acute heart failure ( AHF) composed this study. The National Death Registry was linked to identify the clinical outcomes of all‐cause mortality and cardiovascular death, with a follow‐up duration of up to 4 years. Among a total of 2556 patients (76.4 years of age, 67% men), 360 had on‐admission hyponatremia, defined as a serum sodium level of <135 mEq/L on the first day of hospitalization. On‐admission hyponatremia was a predictor for all‐cause mortality (hazard ratio and 95% CI: 1.43, 1.11–1.83) and cardiovascular mortality (1.50, 1.04–2.17), independent of age, sex, hematocrit, estimated glomerular filtration rate, left ventricular ejection fraction, and prescribed medications. Subjects with severe hyponatremia (<125 mEq/L) would even have worse clinical outcomes. During hospitalization, a drop of sodium levels of >3 mEq/L was associated with a marked increase of mortality than those with minimal or no drop of sodium levels. In addition, subjects with on‐admission hyponatremia and drops of serum sodium levels during hospitalization had an incremental risk of death (2.26, 1.36–3.74), relative to those with normonatremia at admission and no treatment‐related drop of serum sodium level in the fully adjusted model.

Conclusions

On‐admission hyponatremia is an independent predictor for long‐term outcomes in patients hospitalized for AHF. Combined the on‐admission hyponatremia with drops of serum sodium levels during hospitalization may make a better risk assessment in AHF patients.

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Most cited references 21

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Survival after the onset of congestive heart failure in Framingham Heart Study subjects.

K. K. K. Ho, K M Anderson, W Kannel … (1993)

Relatively limited epidemiological data are available regarding the prognosis of congestive heart failure (CHF) and temporal changes in survival after its onset in a population-based setting. Proportional hazards models were used to evaluate the effects of selected clinical variables on survival after the onset of CHF among 652 members of the Framingham Heart Study (51% men; mean age, 70.0 +/- 10.8 years) who developed CHF between 1948 and 1988. Subjects were older at the diagnosis of heart failure in the later decades of this study (mean age at heart failure diagnosis, 57.3 +/- 7.6 years in the 1950s, 65.9 +/- 7.9 years in the 1960s, 71.6 +/- 9.4 years in the 1970s, and 76.4 +/- 10.0 years in the 1980s; p < 0.001). Median survival after the onset of heart failure was 1.7 years in men and 3.2 years in women. Overall, 1-year and 5-year survival rates were 57% and 25% in men and 64% and 38% in women, respectively. Survival was better in women than in men (age-adjusted hazards ratio for mortality, 0.64; 95% CI, 0.54-0.77). Mortality increased with advancing age in both sexes (hazards ratio for men, 1.27 per decade of age; 95% CI, 1.09-1.47; hazards ratio for women, 1.61 per decade of age; 95% CI, 1.37-1.90). Adjusting for age, there was no significant temporal change in the prognosis of CHF during the 40 years of observation (hazards ratio for men for mortality, 1.08 per calendar decade; 95% CI, 0.92-1.27; hazards ratio for women for mortality, 1.02 per calendar decade; 95% CI, 0.83-1.26). CHF remains highly lethal, with better prognosis in women and in younger individuals. Advances in the treatment of hypertension, myocardial ischemia, and valvular heart disease during the four decades of observation did not translate into appreciable improvements in overall survival after the onset of CHF in this large, unselected population.

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Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials.

James Udelson, Mihai Gheorghiade, Karl Swedberg … (2007)

Heart failure causes more than 1 million US hospitalizations yearly, mostly related to congestion. Tolvaptan, an oral, nonpeptide, selective vasopressin V2-receptor antagonist, shows promise in this condition. To evaluate short-term effects of tolvaptan when added to standard therapy in patients hospitalized with heart failure. Two identical prospective, randomized, double-blind, placebo-controlled trials at 359 sites in North America, South America, and Europe were conducted during the inpatient period of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) between October 7, 2003, and February 3, 2006. A total of 2048 (trial A) and 2085 (trial B) patients hospitalized with heart failure and congestion were studied. Patients were randomized to receive either tolvaptan (30 mg/d) or matching placebo, within 48 hours of admission. Primary end point was a composite of changes in global clinical status based on a visual analog scale and body weight at day 7 or discharge if earlier. Secondary end points included dyspnea (day 1), global clinical status (day 7 or discharge), body weight (days 1 and 7 or discharge), and peripheral edema (day 7 or discharge). Rank sum analysis of the composite primary end point showed greater improvement with tolvaptan vs placebo (trial A, mean [SD], 1.06 [0.43] vs 0.99 [0.44]; and trial B, 1.07 [0.42] vs 0.97 [0.43]; both trials P<.001). Mean (SD) body weight reduction was greater with tolvaptan on day 1 (trial A, 1.71 [1.80] vs 0.99 [1.83] kg; P<.001; and trial B, 1.82 [2.01] vs 0.95 [1.85] kg; P<.001) and day 7 or discharge (trial A, 3.35 [3.27] vs 2.73 [3.34] kg; P<.001; and trial B, 3.77 [3.59] vs 2.79 [3.46] kg; P<.001), whereas improvements in global clinical status were not different between groups. More patients receiving tolvaptan (684 [76.7%] and 678 [72.1%] for trial A and trial B, respectively) vs patients receiving placebo (646 [70.6%] and 597 [65.3%], respectively) reported improvement in dyspnea at day 1 (both trials P<.001). Edema at day 7 or discharge improved significantly with tolvaptan in trial B (P = .02) but did not reach significance in trial A (P = .07). Serious adverse event frequencies were similar between groups, without excess renal failure or hypotension. In patients hospitalized with heart failure, oral tolvaptan in addition to standard therapy including diuretics improved many, though not all, heart failure signs and symptoms, without serious adverse events. clinicaltrials.gov Identifier: NCT00071331

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Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry.

Mihai Gheorghiade, William T. Abraham, Nancy M Albert … (2007)

Hyponatraemia has been shown to be an independent predictor of mortality in selected patients with heart failure enrolled in clinical trials. The predictive value of hyponatraemia has not been evaluated in unselected patients hospitalized with heart failure. OPTIMIZE-HF is a registry and performance-improvement programme for patients hospitalized with heart failure and includes a subgroup with 60-90 day follow-up data. The relationship between admission serum sodium concentration and clinical outcomes was analysed in 48,612 patients from 259 hospitals. Admission serum sodium levels were analysed both as a continuous variable and by grouping patients with admission Na or = 135 mmol/L. Patients with hyponatraemia (Na or =135 mmol/L. Patients with hyponatraemia were more likely to be Caucasian, have lower admission systolic blood pressure, and receive intravenous inotropes during hospitalization. Patients with hyponatraemia had significantly higher rates of in-hospital and follow-up mortality and longer hospital stays, although no difference in re-admission rates was observed. After adjusting for differences with multivariable analysis, the risk of in-hospital death increased by 19.5%, the risk of follow-up mortality by 10%, and the risk of death or rehospitalization by 8% for each 3 mmol/L decrease in admission serum sodium below 140 mmol/L. Hyponatraemia in hospitalized patients with heart failure is relatively common and is associated with longer hospital stays and higher in-hospital and early post-discharge mortality. Re-admission rates were equally high in patients with or without hyponatraemia.

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Author and article information

Journal

Journal ID (nlm-ta): J Am Heart Assoc

Journal ID (iso-abbrev): J Am Heart Assoc

Journal ID (doi): 10.1002/(ISSN)2047-9980

Journal ID (publisher-id): JAH3

Journal ID (hwp): ahaoa

Title: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2047-9980

Publication date (Electronic): 23 March 2016

Publication date Collection: March 2016

Volume: 5

Issue: 3 ( doiID: 10.1002/jah3.2016.5.issue-3 )

Electronic Location Identifier: e002668

Affiliations

[ ¹ ] Department of MedicineTaipei Veterans General Hospital TaipeiTaiwan

[ ² ] Department of Medical EducationTaipei Veterans General Hospital TaipeiTaiwan

[ ³ ] Healthcare and Management CenterTaipei Veterans General Hospital TaipeiTaiwan

[ ⁴ ] Cardiovascular Research CenterNational Yang‐Ming University TaipeiTaiwan

[ ⁵ ] Department of MedicineNational Yang‐Ming University TaipeiTaiwan

[ ⁶ ] Institute of Public HealthNational Yang‐Ming University TaipeiTaiwan

Author notes

[*] [* ] Correspondence to: Shih‐Hsien Sung, MD, PhD, Department of Medical Education, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih‐Pai Rd, Taipei, Taiwan. E‐mail: mr.sungsh@ 123456gmail.com

[†]

Wen‐Chung Yu is a co‐corresponding author.

Article

Publisher ID: JAH31411

DOI: 10.1161/JAHA.115.002668

PMC ID: 4943243

PubMed ID: 27009619

SO-VID: e8af4985-1680-4b09-9fe6-4b9af82718a0

License:

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

History

Date received : 16 September 2015

Date accepted : 09 February 2016

Page count

Pages: 8

Funding

Funded by: Taipei Veterans General Hospital

Award ID: V100C‐145

Award ID: V101C‐092

Award ID: V102C‐119

Award ID: and V103B‐017

Funded by: Ministry of Health and Welfare, Taiwan

Award ID: MOHW‐104‐TDU‐B‐211‐113003

Award ID: MOHW‐104‐TDU‐B‐211‐113017

Custom metadata

source-schema-version-number 2.0

component-id jah31411

cover-date March 2016

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:4.8.9 mode:remove_FC converted:05.05.2016

ScienceOpen disciplines: Cardiovascular Medicine

Keywords: acute heart failure,hyponatremia,mortality,biomarkers,heart failure

Data availability:

ScienceOpen disciplines: Cardiovascular Medicine

Keywords: acute heart failure, hyponatremia, mortality, biomarkers, heart failure

Hyponatremia and Worsening Sodium Levels Are Associated With Long‐Term Outcome in Patients Hospitalized for Acute Heart Failure

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Abstract

Background

Methods and Results

Conclusions

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Cardiovascular Innovations and Applications

Most cited references 21

Survival after the onset of congestive heart failure in Framingham Heart Study subjects.

Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials.

Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry.

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